Noncovalent Intracellular Drug Delivery of Hydrophobic Drugs on Au NPs

  • Tennyson Doane
  • Clemens Burda
Part of the Methods in Molecular Biology book series (MIMB, volume 1025)


The successful delivery of hydrophobic drugs to cellular targets continues to present challenges to the pharmaceutical industry. The advances made by nanotechnology have generated new avenues for selectively loading, delivering, and targeting these drugs to their biological targets without compromising efficacy. Here, we describe how gold nanoparticles (Au NPs) functionalized with polyethylene glycol (PEG) can be evaluated for the delivery of hydrophobic drugs in aqueous systems. Specifically, we describe Au NP synthesis, ligand exchange, and delivery evaluation at-the-bench for screening of potential drug candidates.

Key words

Gold nanoparticles Noncovalent drug delivery Ligand exchange Hydrophobic 


  1. 1.
    Ferris DP, Lu J, Gothard C, Yanes R, Thomas CR, Olsen J-C, Stoddart JF, Tamanoi F, Zink JI (2011) Synthesis of biomolecule-modified mesoporous silica nanoparticles for targeted hydrophobic drug delivery to cancer cells. Small 7:1816–1826CrossRefGoogle Scholar
  2. 2.
    Davis ME, Chen Z, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782CrossRefGoogle Scholar
  3. 3.
    Kelkar SS, Reineke TM (2011) Theranostics: combining imaging and therapy. Bioconjugate Chem 22:1879–1903CrossRefGoogle Scholar
  4. 4.
    Burda C, Chen X, Narayanan R, El-Sayed MA (2005) Chemistry and properties of nanocrystals of different shapes. Chem Rev 105:1025–1102CrossRefGoogle Scholar
  5. 5.
    Boal AK, Rotello VM (2000) Fabrication and self-optimization of multivalent receptors on nanoparticle scaffolds. J Am Chem Soc 122:734–735CrossRefGoogle Scholar
  6. 6.
    Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327CrossRefGoogle Scholar
  7. 7.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284CrossRefGoogle Scholar
  8. 8.
    Cheng Y, Samia AC, Meyers JD, Panagopoulos I, Fei B, Burda C (2008) Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer. J Am Chem Soc 130:10643–10647CrossRefGoogle Scholar
  9. 9.
    Kim CK, Ghosh P, Pagliuca C, Zhu Z-J, Menichetti S, Rotello VM (2009) Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. J Am Chem Soc 131:1360–1361CrossRefGoogle Scholar
  10. 10.
    Gref R, Luck M, Quellec P, Marchand M, Dellacherie E, Harnisch S, Blunk T, Muller RH (2000) ’Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B 18:301–313CrossRefGoogle Scholar
  11. 11.
    Lucarini M, Franchi P, Pedulli GF, Pengo P, Scrimin P, Pasquato L (2004) EPR study of dialkyl nitroxides as probes to investigate the exchange of solutes between the ligand shell of monolayers of protected gold nanoparticles and aqueous solutions. J Am Chem Soc 126:9326–9329CrossRefGoogle Scholar
  12. 12.
    Lucarini M, Franchi P, Pedulli GF, Gentilini C, Polizzi S, Pengo P, Scrimin P, Pasquato L (2005) Effect of core size on the partition of organic solutes in the monolayer of water-soluble nanoparticles: an ESR investigation. J Am Chem Soc 127:16384–16385CrossRefGoogle Scholar
  13. 13.
    Turkevich J, Steveson PC, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 11:55–75CrossRefGoogle Scholar
  14. 14.
    Brust M, Walker M, Bethell D, Schiffrin DJ, Whyman R (1994) Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid–liquid system. J Chem Soc Chem 7:801–802CrossRefGoogle Scholar
  15. 15.
    Cheng Y, Samia AC, Li J, Kenney ME, Resnick A, Burda C (2010) Delivery and efficacy of a cancer drug as a function of the bond to the gold nanoparticle surface. Langmuir 26:2248–2255CrossRefGoogle Scholar
  16. 16.
    Prasad BLV, Stoeva SI, Sorensen CM, Klabundae KJ (2002) Digestive ripening of thiolated gold nanoparticles: the effect of alkyl chain length. Langmuir 18:7515–7520CrossRefGoogle Scholar
  17. 17.
    Janda KP, Han H (1996) Combinatorial chemistry: a liquid phase approah. In: Abelson JN (ed) Methods in enzymology, vol 267: combinatorial chemistry. Academic Press, San Diego, CA, p 236 (seen on Googlebooks)Google Scholar
  18. 18.
    Personal Correspondence with Laysan Bio Technical Support (2011)Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Tennyson Doane
    • 1
  • Clemens Burda
    • 1
  1. 1.Case Western Reserve UniversityClevelandUSA

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